Tissue graft materials have attained considerable clinical and economic significance today. It is now well known that collagen-based extracellular matrices (ECMs) derived from warm-blooded vertebrates can be used advantageously as tissue grafts materials. See U.S. Pat. Nos. 4,902,508 and 5,281,422, and International Publication Nos. WO 98/25636 and WO 98/22158. It has been found that collagen-based ECMs can serve as a scaffold on which animal tissues may grow. It has been also found that the materials enhance wound healing, promote endogenous tissue growth, stimulate cell proliferation and induce cell differentiation. Additionally, implants which are made from collagen-based ECMs are absorbed by the body in time and do not have to be removed once applied. The collagen-based ECMs described in the above patents and publications are also characterized by excellent mechanical properties, and effective porosity index which allow them to be used beneficially for vascular graft and connective tissue graft constructs. Furthermore, collagen-based ECMs can be fluidized by comminuting and/or enzymatic digestion, without loss of their apparent positive cell growth promoting properties.
At present, collagen-based ECM materials have been formed into and used as implants and grafts to replace or repair damaged or diseased blood vessels, ligaments, tendons, skin and urinary tract, to name a few examples. Additionally, fluidized ECMs have been proposed for injectable tissue grafts and also for topical applications. See, U.S. Pat. No. 5,275,826 and International Publication No. WO 98/22158. Furthermore, it has been suggested that collagen-based ECMs can be utilized as a cell growth substrate for growing eukaryotic cells in vitro.
Collagen-based ECMs have been harvested from various tissues of warm-blooded vertebrates. To date, various sources for collagen-based ECMs have been identified, including the submucosa of the intestinal, alimentary, respiratory, urinary, genital tracts, and stomachs and the basal membrane of livers of vertebrates. Among the above-mentioned sources, the collagen extracellular component is either an internal layer or a tightly bounded layer of the tissue/organ so that the collagen-based ECM has to be isolated. See U.S. Pat. No. 4,956,178, and International Publication Nos. WO 98/25637 and WO 98/25636. The isolation step generally involves either a de-lamination or a cell dissociation, which complicates the preparatory process and also risks disruption of the native structure of the extracellular component.
In view of the background in this area, there exists a need for collagen-based extracellular matrix materials that are readily isolated and exhibit beneficial properties for applications in tissue grafting, cell growth, and potentially other areas. The present invention addresses these needs.